PMID- 12960960
OWN - NLM
STAT- MEDLINE
DCOM- 20031007
LR  - 20061115
IS  - 0022-2143 (Print)
IS  - 0022-2143 (Linking)
VI  - 142
IP  - 2
DP  - 2003 Aug
TI  - Attenuation by intravenous 2-chloroadenosine of acute lung injury induced by live 
      escherichia coli or latex particles added to endotoxin in the neutropenic state.
PG  - 128-35
AB  - Although neutrophil depletion can reduce the level of acute lung injury (ALI) 
      induced by Escherichia coli endotoxin, that induced by live E coli cannot be 
      attenuated even in neutropenia. This suggests that live E coli cause ALI by way 
      of an mechanism independent of circulating neutrophil. Tumor necrosis 
      factor-alpha (TNF-alpha), which is released from monocytes and macrophages, is a 
      proinflammatory cytokine that is recognized as a central mediator of several 
      forms of inflammation. In this controlled experimental study, we examined the 
      effects of an adenosine-receptor agonist, 2-chloroadenosine (2CA), that has 
      suppressive effects on various cell types and TNF-alpha, on endotoxin plus latex 
      particles, and on ALI induced by live E coli in the neutropenic state. We studied 
      42 guinea pigs rendered neutropenic by means of intraperitoneal cyclophosphamide 
      administration. Experimental groups consisted of (1) a saline-solution control 
      group; (2) an endotoxin (0.2 mg/kg)-treated group; (3) a group treated with 
      endotoxin plus 2CA (10 micro g/kg); (4) a group treated with latex (2 x 
      10(9)/kg); (5) a group exposed to endotoxin and latex; (6) a group exposed to 
      endotoxin, latex, and 2CA; (7) a group exposed to E coli (2 x 10(9)/kg); and (8) 
      a group exposed to E coli and 2CA. The injection of endotoxin alone in 
      neutropenic animals did not increase the indexes of ALI (lung tissue/plasma ratio 
      [T/P] and lung wet weight/dry weight ratio [W/D], calculated with the use of 
      iodine 125-labeled albumin). In contrast, these indexes were increased in the 
      endotoxin-and-latex groups compared with those of the control group. ALI in the 
      endotoxin-and-latex group was attenuated by intravenous 2CA. The intravenous 
      injection of live E coli also caused increases in T/P, W/D, and plasma TNF-alpha, 
      but thse were limited by 2CA. In summary, ALI induced by latex particles added to 
      endotoxin and live E coli in the neutropenic state was attenuated by 2CA, 
      suggesting a partial contribution of various cell types or humoral mediators as a 
      neutrophil-independent pathway in its pathogenesis.
FAU - Sakamaki, Fumio
AU  - Sakamaki F
AD  - Department of Medicine, Cardiopulmonary Division, School of Medicine, Keio 
      University, Japan. sakamaki@tachikawa-hosp.gr.jp
FAU - Ishizaka, Akitoshi
AU  - Ishizaka A
FAU - Urano, Tetsuya
AU  - Urano T
FAU - Sayama, Koichi
AU  - Sayama K
FAU - Nakamura, Hidetoshi
AU  - Nakamura H
FAU - Terashima, Takeshi
AU  - Terashima T
FAU - Waki, Yasuhiro
AU  - Waki Y
FAU - Soejima, Kenzo
AU  - Soejima K
FAU - Tasaka, Sadatomo
AU  - Tasaka S
FAU - Sawafuji, Makoto
AU  - Sawafuji M
FAU - Kobayashi, Kouichi
AU  - Kobayashi K
FAU - Yamaguchi, Kazuhiro
AU  - Yamaguchi K
FAU - Kanazawa, Minoru
AU  - Kanazawa M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lab Clin Med
JT  - The Journal of laboratory and clinical medicine
JID - 0375375
RN  - 0 (Endotoxins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 146-77-0 (2-Chloroadenosine)
RN  - 67924-63-4 (endotoxin, Escherichia coli)
SB  - IM
MH  - 2-Chloroadenosine/*pharmacology
MH  - Acute Disease
MH  - Animals
MH  - Endotoxins/pharmacology
MH  - *Escherichia coli
MH  - Escherichia coli Infections/*immunology
MH  - Guinea Pigs
MH  - Injections, Intravenous
MH  - Lung Diseases/*drug therapy/immunology/microbiology
MH  - Microspheres
MH  - Neutropenia/*immunology/microbiology
MH  - Specific Pathogen-Free Organisms
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2003/09/10 05:00
MHDA- 2003/10/08 05:00
CRDT- 2003/09/10 05:00
PHST- 2003/09/10 05:00 [pubmed]
PHST- 2003/10/08 05:00 [medline]
PHST- 2003/09/10 05:00 [entrez]
AID - S0022214303001057 [pii]
AID - 10.1016/S0022-2143(03)00105-7 [doi]
PST - ppublish
SO  - J Lab Clin Med. 2003 Aug;142(2):128-35. doi: 10.1016/S0022-2143(03)00105-7.